Chronic graft vs. host disease (GVHD) occurs in the majority of survivors of allogeneic hematopoietic cell transplantation (HCT). The syndrome is the major source of non-relapse mortality among two year disease-free survivors, and results in increased symptom burden, functional disability, and impaired quality of life. Therapy of established chronic GVHD is unsuccessful in many cases, and can be associated with toxicity and death due to treatment complications. Rational selection of therapy for any given patient is not possible based on current evidence, and it can be difficult to identify non-responders early in the course of therapy based on clinical judgment. We propose combining cutting edge laboratory techniques with detailed phenotypic data to identify biologic markers predictive of treatment success. The parent R01-funded Chronic GVHD Consortium cohort study will provide rich chronic GVHD response data and allied biospecimens to facilitate this work. In our proposed study, we will identify transcriptional markers of therapeutic response, and verify these findings in an independent patient cohort matched for potentially confounding clinical variables. This work has great promise to identify clinically relevant markers of non-response, and identify mechanisms of therapy resistance that may lead to rational targets for future interventional trials in chronic GVHD.